Page 348 - IJB-10-3

International

Journal of Bioprinting

RESEARCH ARTICLE
A parallel multilayered neurovascular unit-

on-a-chip for modeling neurovascular
microenvironment and screening

chemotherapeutic drugs

Yuanyuan Xu 1,2,3 , Dongsheng Kong , Ting Zhang 1,2,3 *, Zhuo Xiong 1,2,3 *,
4
and Wei Sun 1,2,3,5 *
1 Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing,
China
2 Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Beijing, China
3 Biomanufacturing and Engineering Living Systems Innovation International Talents Base
(111 Base), Beijing, China
4 The First Medical Center of the PLA General Hospital, Beijing, China
5 Department of Mechanical Engineering, Drexel University, Philadelphia, United States of America
(This article belongs to the Special Issue: Bioprinting Process for Tumor Model Development)

Abstract

*Corresponding authors: Humans are grappling with increasing occurrence rate of brain tumors, which
Ting Zhang are associated with unfavorable prognosis and cognitive neurotoxicity caused
(t-zhang@tsinghua.edu.cn) by chemotherapy. Ideally, therapeutic drugs for brain tumors should efficiently
Zhuo Xiong
(xiongzhuo@tsinghua.edu.cn) suppress the tumors while minimizing neurotoxic effects. To facilitate drug
Wei Sun development, in vitro pathological models of human brain tumors are essential.
(weisun@mail.tsinghua.edu.cn) Here, we engineered a sophisticated human neurovascular unit (hNVU) chip
that simulates the microenvironment of pediatric brain using three-dimensional
Citation: Xu Y, Kong D, Zhang T,
Xiong Z, Sun W. A parallel bioprinting technology. The hNVU chip featured a multilayer parallel architecture
multilayered neurovascular unit-on- composed of a biomimetic blood–blood barrier (BBB) and brain region. An
a-chip for modeling neurovascular automated perfusion system in the chip simulated the blood flow within the brain.
microenvironment and screening
chemotherapeutic drugs. The specialized liquid channels within the brain region enabled comprehensive
Int J Bioprint. 2024;10(3):1684. analysis of drug metabolites. The blood–brain barrier (BBB) structure is composed of
doi: 10.36922/ijb.1684 endothelial cells, pericytes, and astrocytes, and the brain region contains endothelial
Received: August 26, 2023 cells, pericytes, astrocytes, microglia, and neural progenitor cells, representing the
Accepted: November 8, 2023 cellular components found in pediatric brain. To replicate the basal membrane, we
Published Online: February 28,
2024 utilized GelMA (gelatin methacryloyl), gelatin, and laminin as primary bioinks, with
the addition of fibrin to mimic the pathological characteristics of brain extracellular
Copyright: © 2024 Author(s).
This is an Open Access article matrix (ECM). The BBB membrane exhibited a maximum electrical resistance of 360
2
distributed under the terms of the Ω cm and demonstrated impressive semipermeability by effectively blocking the
Creative Commons Attribution permeability of large molecules with a molecular weight of 10 kDa. Gene expression
License, permitting distribution,
and reproduction in any medium, analysis and immunofluorescence staining revealed a gradual increase in COL4A1
provided the original work is and fibrin, indicating remodeling of the ECM by the cells. Astrocytoma cells (SF188)
properly cited. were introduced in the model to construct a neurovascular unit containing pediatric
Publisher’s Note: AccScience brain tumor cells. We evaluated the therapeutic effects and toxicity profiles of
Publishing remains neutral with chemotherapeutic drugs, including vorinostat and 5-fluorouracil. Encouragingly,
regard to jurisdictional claims in our investigations revealed that vorinostat not only exhibited remarkable
published maps and institutional
affiliations. tumor-suppressing efficacy but also induced lower neurocognitive toxicity than

Volume 10 Issue 3 (2024) 340 doi: 10.36922/ijb.1684